title: A new role for interferon gamma in neural stem/precursor cell dysregulation.
abstract: BACKGROUND
  The identification of factors that compromise neurogenesis is aimed at improving stem cell-based approaches in the field of regenerative medicine. Interferon gamma (IFNγ) is a main pro-inflammatory cytokine and up-regulated during several neurological diseases. IFNγ is generally thought to beneficially enhance neurogenesis from fetal or adult neural stem/precursor cells (NSPCs).
  
  
  RESULTS
  We now provide direct evidence to the contrary that IFNγ induces a dysfunctional stage in a substantial portion of NSPC-derived progeny in vitro characterized by simultaneous expression of glial fibrillary acid protein (GFAP) and neuronal markers, an abnormal gene expression and a functional phenotype neither typical for neurons nor for mature astrocytes. Dysfunctional development of NSPCs under the influence of IFNγ was finally demonstrated by applying the microelectrode array technology. IFNγ exposure of NSPCs during an initial 7-day proliferation period prevented the subsequent adequate differentiation and formation of functional neuronal networks.
  
  
  CONCLUSIONS
  Our results show that immunocytochemical analyses of NSPC-derived progeny are not necessarily indicating the correct cellular phenotype specifically under inflammatory conditions and that simultaneous expression of neuronal and glial markers rather point to cellular dysregulation. We hypothesize that inhibiting the impact of IFNγ on NSPCs during neurological diseases might contribute to effective neurogenesis and regeneration.
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Moorenstr, 5, 40225 Düsseldorf, Germany. Janine.Walter@googlemail.com.
authors.forename: Janine
authors.initials: J
authors.lastname: Walter
authors.forename: Silke D
authors.initials: SD
authors.lastname: Honsek
authors.forename: Sebastian
authors.initials: S
authors.lastname: Illes
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Wellen
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Christine R
authors.initials: CR
authors.lastname: Rose
authors.forename: Marcel
authors.initials: M
authors.lastname: Dihné